Background:
The objective of this study was to describe thrombin generation in children undergoing cardiac surgery with cardiopulmonary bypass (CPB). Change in the endogenous thrombin potential (ETP) across three measurements before and after CPB (after protamine and at chest closure) was the primary outcome. Secondary analyses explored an association between thrombin generation and transfusion requirements and predictors of the thrombin generation decline.
Methods:
Blood samples of children (median age 6.3 months; 68.5% weighed <10 kg) were collected intraoperatively three times: before administration of heparin (baseline), shortly after protamine and at sternal closure. Platelet poor plasma obtained after centrifugation of these samples was frozen at -80ºC. Thrombin generation and anti-Xa assays were performed in series on batches of thawed samples to evaluate thrombin generation parameters and functional activity of unfractionated heparin which could have affected thrombin generation assay results.
Results:
Between August 2022 and May 2024, 162 plasma samples from 54 patients were collected and analyzed. Compared with baseline, mean ETP decreased by 1911 nM (95% CI 1655 to 2168) after administration of protamine, and by 1865 nM (95% CI 1609 to 2122) at sternal closure, P<0.001. Similar changes were observed in secondary thrombin generation parameters. Median unfractionated heparin activity was <0.1 U/ml at all three time points. Secondary analyses showed strong negative correlation between ETP after protamine and volume of transfusion after bypass (ρ =-0.52, P<0.001). Among five examined factors, only total heparin dose was independently associated with ETP decline, with higher dose being predictive of greater ETP decline (P=0.002).
Conclusions:
In children undergoing cardiac surgery, we noted a significant and persistent decline in endogenous thrombin potential following cardiopulmonary bypass, despite hemostatic interventions. This reduced thrombin potential correlated with higher volume of transfusions. Additionally, greater intraoperative heparin requirements could be linked to a more pronounced decline in thrombin generation.